Bispecific antibodies to IL-23 and IL-17A/F

Abstract

The present invention relates to antagonizing the activity of IL-17A, IL-17F and IL-23 using bispecific antibodies that comprise a binding entity that is cross-reactive for IL-17A and IL-17F and a binding entity that binds IL-23p19. The present invention relates to novel bispecific antibody formats and methods of using the same.

What is claimed is: 
     
       1. An isolated bispecific antibody comprising an IL-17A/F binding entity and an IL-23 binding entity, wherein the IL-23 binding entity comprises two pairs of immunoglobulin chains, each pair having one light and one heavy chain, which light chain variable domain comprises a CDR1 having the amino acid sequence of SEQ ID NO:22, a CDR2 having the amino acid sequence of SEQ ID NO:23, and a CDR3 having the amino acid sequence of SEQ ID NO:24, and heavy chain variable domain comprises a CDR1 having the amino acid sequence of SEQ ID NO:19, a CDR2 having the amino acid sequence of SEQ ID NO:20, and a CDR3 having the amino acid sequence of SEQ ID NO:21, and wherein the IL-17A/F binding entity comprises two Fab fragments which are linked to the C-termini of the heavy chains of the IL-23 binding entity. 
     
     
       2. The bispecific antibody of  claim 1 , wherein the light chains of the Fab of the IL-17A/F binding entity and the IL-23 binding entity comprise a variable domain comprising the amino acid sequence of SEQ ID NO:9. 
     
     
       3. The bispecific antibody of  claim 1 , wherein the light chains of the Fab of the IL-17A/F binding entity and the IL-23 binding entity comprise a constant domain comprising the amino acid sequence of SEQ ID NO:10. 
     
     
       4. The bispecific antibody of  claim 1 , wherein the light chains of the Fab of the IL-17A/F binding entity and the IL-23 binding entity comprise a variable domain comprising the amino acid sequence of SEQ ID NO:9 and a constant domain comprising the amino acid sequence of SEQ ID NO:10. 
     
     
       5. The bispecific antibody of  claim 1 , wherein the heavy chain variable domain of the IL-23 binding entity comprises the amino acid sequence of SEQ ID NO:7. 
     
     
       6. The bispecific antibody of  claim 1 , wherein the heavy chain constant domain of the IL-23 binding entity comprises the amino acid sequence of SEQ ID NO:8 or amino acid residues 1-326 of SEQ ID NO:8. 
     
     
       7. The bispecific antibody of  claim 1 , wherein the heavy chain variable domain of the Fab of the IL-17A/F binding entity comprises a CDR1 having the amino acid sequence of SEQ ID NO:25, a CDR2 having the amino acid sequence of SEQ ID NO:26, and a CDR3 having the amino acid sequence of SEQ ID NO:27, and wherein the light chain variable domain of the Fab of the IL-17A/F binding entity comprises a CDR1 having the amino acid sequence of SEQ ID NO:22, a CDR2 having the amino acid sequence of SEQ ID NO:23, and a CDR3 having the amino acid sequence of SEQ ID NO:24. 
     
     
       8. The bispecific antibody of  claim 1 , wherein the heavy chain variable domain of the Fab of the IL-17A/F binding entity comprises the amino acid sequence of SEQ ID NO:13. 
     
     
       9. The bispecific antibody of  claim 1 , wherein the heavy chain C H1  of the Fab of the IL-17A/F binding entity comprises the amino acid sequence of SEQ ID NO:15. 
     
     
       10. A composition comprising the bispecific antibody according to  claim 1 , and a pharmaceutically acceptable carrier. 
     
     
       11. An isolated monoclonal antibody or antigen-binding fragment thereof that specifically binds to IL-17A (SEQ ID NO:2) and IL-17F (SEQ ID NO:4) comprising a heavy chain variable domain and a light chain variable domain, wherein the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO:13 and the light chain variable domain comprises the amino acid sequence of SEQ ID NO:9. 
     
     
       12. An isolated monoclonal antibody or antigen-binding fragment thereof that specifically binds to IL-23p19 (SEQ ID NO:6) comprising a heavy chain variable domain and a light chain variable domain, wherein the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO:7, and wherein the light chain variable domain comprises the amino acid sequence of SEQ ID NO:9.